Preimmunization with a heat-killed preparation of Mycobacterium vaccae enhances fear extinction in the fear-potentiated startle paradigm
Abstract
The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits, and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for trauma-related, anxiety, and affective disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience. Traumatic experiences can lead to long-lasting fear memories and exaggerated fear potentiation of the acoustic startle reflex. The acoustic startle reflex is an ethologically relevant reflex and can be potentiated in both humans and rats through Pavlovian conditioning. Mycobacterium vaccae NCTC 11659 is a soil-derived bacterium with immunoregulatory and anti-inflammatory properties that has been demonstrated to confer stress resilience in mice. Here we immunized adult male Sprague Dawley rats 3×, once per week, with a heat-killed preparation of M. vaccae NCTC 11659 (0.1mg, s.c., in 100µl borate-buffered saline) or vehicle, and, then, 3weeks following the final immunization, tested them in the fear-potentiated startle paradigm; controls were maintained under home cage control conditions throughout the experiment (n=11-12 per group). Rats were tested on days 1 and 2 for baseline acoustic startle, received fear conditioning on days 3 and 4, and un…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Heat-killed Mycobacterium vaccae accelerates extinction learning in adult rats.
“whereas heat-killed Mycobacterium vaccae has the opposite effect, accelerating extinction learning in adult rats (Fox et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Fox et al., 2017
Cites
Molecular biology of 5-HT receptors
Hannon, J., & Hoyer, D. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.03.020 · Cited by 815 · see citing works
Hodes, G. E., Pfau, M. L., Leboeuf, M., Golden, S. A., Christoffel, D. J., Bregman, D., Rebusi, N., Heshmati, M., Aleyasin, H., Warren, B. L., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415191111 · Cited by 692 · see citing works
Norrholm, S. D., Jovanovic, T., Olin, I. W., Sands, L. A., Karapanou, I., Bradley, B., & Ressler, K. J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.013 · Cited by 397 · see citing works
Assessment of Plasma C-Reactive Protein as a Biomarker of Posttraumatic Stress Disorder Risk
Eraly, S. A., Nievergelt, C. M., Maihofer, A. X., Barkauskas, D. A., Biswas, N., Agorastos, A., O’Connor, D. T., & Baker, D. G. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.4374 · Cited by 386 · see citing works
Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder
Hoge, E. A., Brandstetter, K., Moshier, S., Pollack, M. H., Wong, K. K., & Simon, N. M. (2009) · Depression and Anxiety · doi:10.1002/da.20564 · Cited by 343 · see citing works
Redefining the serotonergic system by genetic lineage
Jensen, P., Farago, A. F., Awatramani, R. B., Scott, M. M., Deneris, E. S., & Dymecki, S. M. (2008) · Nature Neuroscience · doi:10.1038/nn2050 · Cited by 244 · see citing works
Substantial reduction of naïve and regulatory T cells following traumatic stress
Sommershof, A., Aichinger, H., Engler, H., Adenauer, H., Catani, C., Boneberg, E.-M., Elbert, T., Groettrup, M., & Kolassa, I.-T. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.07.003 · Cited by 172 · see citing works
Maier, S. F. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.09.003 · Cited by 143 · see citing works
Study on serum cytokine levels in posttraumatic stress disorder patients
Guo, M., Liu, T., Guo, J.-C., Jiang, X.-L., Chen, F., & Gao, Y.-S. (2012) · Asian Pacific Journal of Tropical Medicine · doi:10.1016/s1995-7645(12)60048-0 · Cited by 113 · see citing works
Distinct transcriptomes define rostral and caudal serotonin neurons
Wylie, C. J., Hendricks, T. J., Zhang, B., Wang, L., Lu, P., Leahy, P., Fox, S., Maeno, H., & Deneris, E. S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4656-09.2010 · Cited by 104 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Embracing diversity in the 5-HT neuronal system
Okaty, B. W., Commons, K. G., & Dymecki, S. M. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0151-3 · Cited by 319 · see citing works
A Global Survey of Mycobacterial Diversity in Soil
Walsh, C. M., Gebert, M. J., Delgado-Baquerizo, M., Maestre, F. T., & Fierer, N. (2019) · Applied and Environmental Microbiology · doi:10.1128/aem.01180-19 · Cited by 111 · see citing works
Sun, Y., Geng, W., Pan, Y., Wang, J., Xiao, P., & Wang, Y. (2019) · Food & Function · doi:10.1039/c8fo02096e · Cited by 89 · see citing works
Kelly, J. R., Keane, V. O., Cryan, J. F., Clarke, G., & Dinan, T. G. (2019) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2019.04.006 · Cited by 65 · see citing works
- Authors
- Fox, J. H., Hassell, J. E., Siebler, P. H., Arnold, M. R., Lamb, A. K., Smith, D. G., Day, H. E. W., Smith, T. M., Simmerman, E. M., Outzen, A. A., Holmes, K. S., Brazell, C. J., & Lowry, C. A.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Lowry, Christopher A.
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 66
- Pages
- 70-84
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2751000579
- Cited by
- 44
- References
- 10
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 11 · 2018: 7 · 2017: 3
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- Mycobacterium vaccae, fear extinction, fear-potentiated startle, acoustic startle response, serotonergic signaling, dorsal raphe nucleus, median raphe nucleus, tryptophan hydroxylase 2, 5-HT1A receptor, serotonin transporter, SLC22A3, post-traumatic stress disorder, hygiene hypothesis, immune regulation
- MeSH terms
- Organic Cation Transporter 3, Animals, Bacterial Vaccines, Brain, Conditioning, Classical, Extinction, Psychological, Fear, Immunization, Male, Mycobacterium, RNA, Messenger, Serotonin, Reflex, Startle, Stress, Psychological, Tryptophan Hydroxylase, Vaccines, Inactivated, Rats, Sprague-Dawley, Organic Cation Transport Proteins, Receptor, Serotonin, 5-HT1A, Serotonin Plasma Membrane Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review